Environmental Modifications in sub-Saharan Africa: Changing Epidemiology, Transmission and Pathogenesis of Plasmodium falciparum and P. vivax Malaria PROGRAM SUMMARY Chronic hunger, food insecurity and famine continue to affect millions of residents of sub- Saharan Africa. Most people in African countries depend on rain-fed agriculture, making these populations vulnerable to drought and famine. Construction of dams and initiating rural irrigation schemes has been widely recognized as key solutions to food security and economic growth in drought prone regions. In the past decade, sub-Saharan African countries have experienced a new era of large dam constructions and expansion of irrigated agricultural farms. These environmental changes may have unforeseen ecologic consequences that adversely affect human health. However, to date there has been limited basic or translational research to evaluate the impact of water resource development and shifting agricultural practices on malaria ecosystems and attendant changes in the epidemiology, transmission, and pathogenesis of malaria. To address the major knowledge gaps and challenges in malaria control and elimination in the face of drastic environmental modifications in sub-Saharan Africa, our ICEMR established a consortium with outstanding institutions and investigators from the US, Australia, Kenya and Ethiopia to study scientific questions important to the global malaria control and elimination effort, especially to the countries in the Greater Horn of Africa. The overarching goal of this ICEMR project is to assess the impact of human-induced environmental modifications such as dam construction, irrigation and shifting agricultural practices on the epidemiology, transmission, pathogenesis and immunology of Plasmodium falciparum and P. vivax malaria in highly populated Kenya and Ethiopia where major investments in water resource development projects are taking place. The ICEMR has three projects, each with multiple specific objectives. Project 1 will assess the impact of environmental modifications from water resource development projects on P. falciparum and P. vivax malaria epidemiology at the molecular, individual, field and population levels. Project 2 will examine the impact of environmental modifications on vector ecology and transmission, the outcomes of which will inform new integrated vector control approaches. Project 3 aims to determine the impact of environmental modifications on malaria pathogenesis and immunity by elucidating the immune mechanisms underlying susceptibility to symptomatic malaria and evaluating humoral immunity to gametocytes. The administrative and data management cores will provide support to the entire program. Knowledge gained from this ICEMR is important to malaria control, not only for the two study countries studied, but also to other regions of Africa prone to drought, famine, and large scale human population movement.